DMD-Associated Dilated Cardiomyopathy
Conditions
Brief summary
This research study is testing whether an experimental drug, called SRD-001, is safe and helps the weakened heart of patients with Duchenne muscular dystrophy (DMD) regain its ability to effectively pump blood to the rest of the body. SRD-001 is a form of gene therapy. The goal of SRD-001 gene therapy is to provide the heart muscle cells with extra copies of the SERCA2a gene so that they can produce more SERCA2a protein to help the heart muscle cells squeeze/contract better. Researchers will compare SRD-001 treated participants with no-treatment participants; all participants will continue to take their current heart medications. All participants will be followed very closely for 2 years and undergo cardiac magnetic resonance imaging of their heart at baseline, year 1 and year 2 along with assessment of upper limb function and lung function. After the 2 years of close follow-up, all participants will roll over into long-term follow-up where they will be called biannually for information on their current medical status.
Detailed description
This phase 1b, multi-center, non-randomized, open-label, ascending dose escalation, no-intervention-control trial will assess the safety and explore the efficacy of SRD-001 administered as a one-time antegrade epicardial coronary artery infusion for the treatment of participants with cardiomyopathy secondary to DMD. SRD-001 is an AAV1 vector expressing the transgene for SERCA2a. Twelve participants will be assigned to either active treatment with SRD-001 or no-intervention based upon their neutralizing antibody status. The objectives of the trial are (1) to evaluate the safety of a one-time intracoronary administration of SRD-001 in participants with cardiomyopathy due to DMD; and (2) to explore the impact of SRD-001 on heart and skeletal muscle function and quality of life. After screening to determine eligibility, participants will be sequentially assigned to low dose SRD-001, high dose SRD-001 or no-intervention. Participants assigned to active treatment with SRD-001 will under cardiac catheterization and angiography just prior to the intracoronary infusion of SRD-001 and spend overnight int he hospital for observation.
Interventions
GENETICSRD-001
SRD-001 is an adeno-associated virus serotype 1 (AAV1) based gene therapy designed to deliver a copy of the gene encoding the human sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a). It is administered as a one-time intracoronary infusion.
Sponsors
Sardocor Corp.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of DMD with confirmatory genetic testing * Cardiomyopathy with left ventricular scar in at least 3 of 16 segments * Left ventricular ejection fraction \< 40% * Individualized, optimized cardiac medical therapy and glucocorticoid treatment for at least 12 months prior to enrollment * Willing and able to provide informed consent
Exclusion criteria
* Abnormal blood pressure * Non-DMD-related liver function test elevations * Cystatin C ≥ 1.2 mg/L * Thrombocytopenia * Anemia * Inadequate pulmonary function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of cell-mediated immune reaction | From Day 1 to Week 52 | Cell-mediated immune reaction as assessed by enzyme-linked immunosorbent spot (ELISpot) |
| Rate of all-cause mortality | From Day 1 to Week 52 and Week 104 | Death |
| Rate and severity of all treatment-emergent adverse events | From Day 1 to Week 52 and Week 104 | Adverse events |
| Rate and severity of related treatment-emergent adverse events | From Day 1 to Week 52 and Week 104 | Adverse events related to the investigational product or the administration procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change, including normal/abnormal shifts, in laboratory evaluations | From Day 1 to Week 52 and Week 104 | Hematology, serum chemistries, urinalysis, cardiac enzymes and anti-AAV1 antibodies |
| Change, including normal/abnormal shifts, in 12-lead electrocardiogram (ECG) | From Day 1 to Week 52 and Week 104 | Change in the heart's electrical activity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in myocardium and left ventricular structure and function | From baseline to Week 52 and Week 104 | Assessed by cardiac magnetic resonance imaging with late gadolinium enhancement |
| Change in quality of life | From baseline to Week 52 and Week 104 | Assessed by the Duchenne muscular dystrophy quality of life questionnaire |
| Change in pulmonary function | From baseline to Week 52 and Week 104 | Assessed by slow vital capacity, forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, maximum inspiratory pressure, maximum expiratory pressure, peak cough flow and inspiratory flow reserve |
| Change in skeletal muscle function | From baseline to Week 52 and Week 104 | Assessed by PUL 2.0, grip strength, key and tip-to-tip pinch strength and elbow flexion strength |
Countries
United States
Contacts
Primary ContactSardocor Corp.
Outcome results
None listed